Process for the preparation of esters of aromatic n, n-dialkylaminocarboxylic acids



United States Patent 3,413,334 PROCESS FOR THE PREPARATION OF ESTERS OFAROMATIC N,N-DIALKYLAMINOCARBOXYLIC ACIDS Rudolf Burkhardt and HelmutWulif, Witten (Ruhr), Germany, assignors to Chemische Werke WittenG.m.b.H., Witten (Ruhr), Germany No Drawing. Filed Oct. 25, 1965, Ser.No. 505,196 Claims priority, application Ester-many, Dec. 9, 1964,

8 Claims. of. 260471) ABSTRACT OF THE DISCLOSURE This invention relatesto the preparation of esters. More particularly, it relates to a processfor the preparation of eters of aromatic dicarboxylic acids. Even moreparticularly, the invention relates to a process for the preparation ofesters of aromatic N,N-dialkylaminocarboxylic acids.

Aromatic N,N-dialkylaminocarboxylic acids, wherein both the dialkylaminogroups and the carboxylic groups are linked directly to the aromaticresidue, may be prepared by the oxidation of aromaticN,N-dialkylaminoaldehydes or aromatic N,N-dialkylamines having one ormore methyl groups substituted in the aromatic nucleus thereof, by thecarboxylation of aromatic N,N-dialkylamines with phosgene or carbondioxide and Grignard compounds, or by the alkylation of the amino groupof aromatic aminocarboxylic acids. Of greatest significance among thesevarious methods of preparation is the lastmentioned N-alkylation whichis carried out under reducing conditions either with the use ofconventional alkylation agents or with aliphatic aldehydes.

It is known in the prior art to prepare p-dialkylaminobenzoic acid alkylesters by the reductive alkylation of p-aminobenzoic acid esters withaliphatic aldehydes. This reduction is carried out with hydrogen in thepresence of hydrogenation catalysts and, if desired, other supplementarycatalysts, or with zinc and acetic acid. Yields of 30 to 60% have beenobtained with this process.

More general applicability has been attained with the N-alkylationprocess wherein known alkylation agents were employed. Exemplary of suchare the reactive alkyl halides, particularly alkyl iodides, dialkylsulfates and the alkyl esters of benzenesulfonic acid andp-toluenesulfonic acid. The reaction of these compounds with amino acidsor the esters thereof produces both monoand dialkylated products. It isnecessary to use a more or less significant excess of alkylation agentsin order to increase the yield of dialkylamino compounds. However, thismay, in turn, lead to the formation of undesirable trialkyl ammoniumsalts and/or betaine. While alkyl iodides and alkyl esters of aromaticsulfonic acids are of great importance in preparing such compounds, theyhave been found to be unsuitable on a commercial or technical basisbecause of reasons of economics. Furthermore, the alkyl bromides canonly be used to a limited extent because of their low reactivity. Hence,dialkyl sulfates have chiefly been employed for such alkylations on alarge or technical scale.

The aliphatic alcohols which are utilized to a large extent for thealkylation of ammonia and amines must also be considered as alkylationagents. Very little has been done in the prior art With regard to usingthe processes conventional With such alkylation agents in connectionwiththe alkylation of the aromatic aminocarboxylic acids and the estersthereof, since these compounds are sensitive to high temperatures andacid catalysts. For example, when paminobenzoicacid is alkylated withethanol in the presence of Raney nickel, only the monoethylatedcompound, while very little or no p-diethylaminobenzoic acid, isobtained.

One of the objects of the present invention is to provide an improvedprocess for the preparation of esters of aromaticN,N-dialkylaminocarboxylic acids which overcomes the disadvantages anddeficiencies of the prior art methods.

Another object of the present invention is to provide a process for thepreparation of esters of aromatic N,N- dialkylaminocarboxylic acidswhich may be carried out in an efficacious and simple manner.

A further object of the present invention is to provide an improvedprocess for the preparation of esters of aromaticN,N-dialkylaminocarboxylic acids which may be carried out on anindustrial scale.

A still further object of the invention is to provide a process for thepreparation of esters of aromatic N,N- dialkylaminocarboxylic acidswhich may be carried out economically and effectively on a large scale.

These and other objects of the present invention Will become apparent tothose skilled in the art from a reading of the following specificationand claims.

In accordance with the present invention, it has been found that alkylesters of aromatic N,N-dialky1aminocarboxylic acids having the generalformula wherein Ar is either a monoor polynuclear or, if desired, analkyl-substituted aromatic residue, R is an alkyl residue having 1 to 3carbon atoms, R is an alkyl residue which may be the same or differentfrom R, and n is a whole number from 1 to 3 may be obtained from thecorresponding aminocarboxylic acid esters by heating the same withaliphatic alcohols containing from 1 to 3 carbon atoms in the moleculein the presence of catalytic quantities of iodine or low molecularWeight alkyl iodides. The reaction is carried out effectively underpressure at a temperature of from about to 250 C. Further treatment ofthe reaction mixture is carried out in a conventional manner.

The process according to the present invention renders the preparationof N,N-dialkylaminocarboxylic acid esters possible with the use ofaliphatic alcohols. Therefore, the process may be carried outconsiderably more economically than alkylation processes using otheralkylation agents, including compounds mentioned hereinabove such as thedialkyl sulfates and aliphatic aldehydes. Hence, it is possible to carryout the process of the preent invention easily on a large technicalscale. For example, as compared to reductive alkylation with aldehyde,the process of the present invention has the advantage that reducingagents are not required in order to carry out the process.

Any of the suitable alkyl esters of aromatic aminocarboxylic acids maybe used as a starting material in the process of the present invention.These may be obtained, for example, by reduction of the correspondingnitro-compounds. Exemplary of such starting materials are compounds suchas the methyl esters of 3-aminobenzoic acid and of S-aminoisophthalicacid. These compounds are easily obtained by the nitration of thebenzoic and, respectively, the isophthalic acid methyl esters and by thesubsequent catalytic reduction thereof. Aromatic aminocarboxylic alkylesters substituted with one or more than one alkyl group in the aromaticnucleus may also be employed. Alkyl herein is meant to refer to at leastlower alkyl, defined hereinbelow, but is not to be limited thereto,i.e., when suitable, higher alkyl homologs are included.

Methanol is the preferred aliphatic alcohol to be employed in theprocess of the present invention, since it is often preferred tointroduce methyl groups during the alkylation reaction. However, otheraliphatic alcohols may be employed as the alkylation agents herein, forexample, ethanol and l-propanol. These three alcohols are especiallysuitable for the N-alkylation process of the present invention, andwhile higher alcohols also act in an alkylating manner, they tend tolead to the formation of monoalkylated products because of stericconsiderations arising from their overall bulkiness.

Suitable cataylsts to be employed in the process of the presentinvention include elemental iodine and lower alkyl iodides. By loweralkyl is means herein alkyl groups containing from 1 to 4 carbon atoms,i.e., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl andt-butyl. These catalysts may be employed in amounts of from about 0.005to 0.05 mole per mole of aminocarboxylic acid ester.

The reaction takes place effectively with a temperature range of fromabout 150 to 250 C. The preferred reaction temperature range is :fromabout 180 to 230 C. The particular choice of the reaction temperaturedepends upon the thermal stability of the aminocarboxylic acid estersand can be easily adjusted in accordance therewith by one skilled in theart.

Aromatic dialkylaminocarboxylic acid-s and the esters thereof arecompounds having known utilities in the prior art. For example, they maybe used for modifying polycondensation products. The methyl esters areparticularly useful in this regard and may be used as component parts ofthe molecular chains in linear polyesters in order to improve thedyeability and the electrostatic properties thereof. As components ofunsaturated polyester resins, these compounds accelerate the hardeningthereof and, therefore, make it possible to cold-harden these resins. Inaddition, the aromatic esters produced by the process of the presentinvention may be used to prepare valuable chemical substances such asdrugs and dyestuffs. Their properties of luminescence and of absorbingultraviolet rays may also 'be used to advantage.

The following examples are .given merely as illustrative of the presentinvention and are not be be considered as limiting thereof.

Example I 124 grams (0.75 mole) of ethyl p-aminobenzoate together with500 ml. of ethanol and 3 grams of ethyl iodide are maintained in anautoclave for five hours at ZOO-205 C. The reaction mixture is stirredfor 15 minutes with the addition of 300 ml. of benzene and 5 grams ofanhydrous sodium carbonate and filtered. Benzene, excess ethanol andwater formed during the reaction are distilled out of the filtrate. Theliquid brown residue is distilled under vacuum. After distilling off asmall preliminary run consisting mainly of diethylaniline, there isobtained, at 1.2 torr and at a temperature of 132 to 138 C., 125 gramsof ethyl p-(N,N-diethylamino)-benzoate. This corresponds to a yield of75.3%. The product solidifies while cooling to crystals having a meltingpoint of 43 C.

Example II 419 grams (2 moles) of methyl S-aminoisophthalate, 2 litersof methanol and 8 grams of iodine are heated in an autoclave to 205-210C. for five hours. The brownish crystals obtained are suctioned out ofthe reaction product and recrystallized from 3 liters of methanol withthe addition of activated carbon thereto. Obtained is 300 grams ofalmost colorless crystals having a melting point of C. By mixing themother liquors back with the crystals and recrystallizing, another 92grams of product having a melting point of 124.5 C. is obtained. Thetotal yield of 392 grams of dimethyl 5-(N,N- dimethylamino)-isophthalatecorresponds to a yield of 82.6%.

Example III The reaction mixture obtained by heating 100 grams of2-methyl5-aminonaphthoate, 500 ml. of methanol and 2 grams of iodine to200 C. for five hours is treated as described in Example I. During thedistillation thereof, 79.5 grams of2-methyl-5-(N,N-dimethyl'amino)-naphthoate is obtained as the mainfraction. This product passes over as a faintly brownish oil at to C.under a pressure of 0.1 torr. This amount of product represents a 66.5%theoretical yield.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention and all suchmodifications are intended to be included within the scope of thefollowing claims.

We claim:

1. A process for the preparation of alkyl esters of aromaticN,N-dialkylaminocarboxylic acids having the formula (R) NAr(COOR')wherein Ar is a mononuclear aromatic nucleus, a polynuclear aromaticnucleus, an alkyl-substituted mononuclear aromatic nucleus or analkyl-substituted polynuclear aromatic nucleus, R and R are alkyl groupsand n is a whole number from 1 to 3, which comprises reacting thecorresponding aromatic aminocarboxylic acid ester with an alkanol havingfrom 1 to 3 carbon atoms in the presence of a catalytic amount of iodineor a lower alkyl iodide at a temperature of from about 150 to 250 C.

2. The process of claim 1, wherein said alkanol is methanol.

3. The process of claim 1, wherein the reaction is carried out underpressure.

4. The process of claim 1, wherein the reaction is carried out at atemperature of from about 180 to 230 C.

5. The process of claim 1, wherein said iodine or lower alkyl iodide isemployed in amounts of from about 0.005 to 0.05 mole per mole ofaminocarboxylic acid ester.

6. A process for the preparation of alkyl esters of aromaticN,N-dialkylaminocarboxylic acids having the formula (R) NAr(COOR)wherein Ar is a mononuclear aromatic nucleus, a polynuclear aromaticnucleus, an alkyl-substituted mononuclear aromatic nucleus or analkyl-substituted polynuclear aromatic nucleus, R is an alkyl grouphaving from 1 to 3 carbon atoms, R is an alkyl group and n is a wholenumber from 1 to 3, which comprises reacting the corresponding aromaticaminocarboxylic acid ester with an alkanol having from 1 to 3 carbonatoms at a temperature of from about 150 to 250 C. in the presence offrom about 0.005 to 0.05 mole per mole of aminocarboxylic acid ester ofiodine or a lower alkyl iodide.

7. The process of claim 6, wherein said alkanol is methanol.

8. The process of claim 6, wherein the reaction is carried out underpressure.

References Cited Advanced Organic Chemistry, by Royals (Prentice Hall)1956, pp. 467 and 468 recited.

LORRAINE A. WEINBERGER, Primary Examiner.

A. THAXTON, Assistant Examiner.

